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土耳其代尼兹利省人类多药耐药(MDR1)基因C3435T多态性的基因型和等位基因频率

Genotype and allele frequency of human multidrug resistance (MDR1) gene C3435T polymorphism in Denizli province of Turkey.

作者信息

Turgut Sebahat, Turgut Günfer, Atalay Erol Omer

机构信息

Department of Physiology, Medical Faculty, Pamukkale University, 20070, Denizli, Turkey.

出版信息

Mol Biol Rep. 2006 Dec;33(4):295-300. doi: 10.1007/s11033-006-9022-x. Epub 2006 Nov 2.

Abstract

Human p-glycoprotein encoded by human multidrug resistance (MDR1) gene, is a transmembrane protein that serves as efflux pump for a wide variety of lipophilic compounds possessing a physiological role in protecting cells against the DNA damaging of certain xenobiotics. According to the published data, the frequency of C3435T polymorphism differs depending on the different ethnical populations such as Asian, African, and Caucasians populations. In our study, we identified the MDR1 C3435T polymorphism in 150 healthy volunteers in Denizli province of Turkey. DNA was extracted from peripheral blood samples by standard phenol/chloroform extraction method. Polymerase chain reaction-restriction fragment length polymorphism was used for the detection of C3435T single nucleotide polymorphism. We obtained CC, CT and TT genotype frequencies as 20, 53 and 27%, respectively. According to our results, the C allele in Turkish population (Denizli province, west of Turkey) is found 47% and this data shows similarity with Caucasian (UK and German) populations and significantly lower than African populations (p < 0.001). Our study is the first data on the genotype and allele frequency of the human multidrug resistance (MDR1) Gene C3435T Polymorphism in Denizli Province at regional basis in Turkey. Our results could serve as a basis for large-scale correlation studies on the relevance of C3435T genotype in cancer therapy and other diseases in Turkish population. Investigation of genotype frequencies related with p-glycoprotein substrates should be investigated in large scale at regional bases in Turkish population. The scaled-up data might help either to the use of p-glycoprotein substrates to be used for therapeutic applications and population genetics considering the genotype frequencies possibly occurring throughout the history in Anatolian basin.

摘要

人类多药耐药(MDR1)基因编码的人P-糖蛋白是一种跨膜蛋白,作为多种亲脂性化合物的外排泵,在保护细胞免受某些异生物素的DNA损伤方面具有生理作用。根据已发表的数据,C3435T多态性的频率因不同种族群体(如亚洲、非洲和白种人群体)而异。在我们的研究中,我们在土耳其代尼兹利省的150名健康志愿者中鉴定了MDR1 C3435T多态性。通过标准酚/氯仿提取法从外周血样本中提取DNA。采用聚合酶链反应-限制性片段长度多态性方法检测C3435T单核苷酸多态性。我们获得的CC、CT和TT基因型频率分别为20%、53%和27%。根据我们的结果,土耳其人群(土耳其西部代尼兹利省)中C等位基因的比例为47%,这一数据与白种人(英国和德国)群体相似,且显著低于非洲人群(p<0.001)。我们的研究是土耳其代尼兹利省区域范围内关于人类多药耐药(MDR1)基因C3435T多态性基因型和等位基因频率的首个数据。我们的结果可为土耳其人群中C3435T基因型与癌症治疗及其他疾病相关性的大规模关联研究提供依据。应在土耳其人群的区域范围内大规模研究与P-糖蛋白底物相关的基因型频率。扩大规模的数据可能有助于考虑安纳托利亚盆地历史上可能出现的基因型频率,将P-糖蛋白底物用于治疗应用和群体遗传学研究。

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